Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0282612 (
PIN
)
2,291
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
PIN
, an 89-amino-acid polypeptide found in a rat hippocampal cDNA library using the yeast two-hybrid system and various neuronal nitric oxide synthase (nNOS) fragments as bait, was reported to be an inhibitor of nNOS (Science 274, 774-778, 1996).
PIN
reportedly inhibited nNOS selectively and did not interact with either the endothelial or
inducible nitric oxide synthase
isoforms. Inhibition was attributed to the ability of
PIN
to dissociate the catalytically active nNOS homodimer.
PIN
is a dynein light chain (J. Biol. Chem. 271, 19358-19366, 1996), which suggested that
PIN
may serve as an axonal transport protein for nNOS. We have synthesized a rat
PIN
cDNA by recursive polymerase chain reaction and have expressed the protein in Escherichia coli. Recombinant
PIN
is a folded dimeric, mostly alpha-helical protein with a single deeply buried tryptophan residue. We have also expressed and purified the nNOS fragment to which
PIN
reportedly binds (residues 163-245). This recombinant peptide has a disordered secondary structure. Gel-filtration experiments show that
PIN
binds to both the full-length nNOS and nNOS fragment. However,
PIN
neither inhibits nNOS activity nor dissociates the nNOS dimer into monomeric species.
PIN
thus possibly functions as a dynein light chain involved in nNOS axonal transport but is not an inhibitor of the enzyme. Our results agree with the proposal (Cell 82, 743-752, 1995) that the
PIN
recognition sequence in nNOS both lies outside the catalytic core and is not part of the monomer-monomer contact region.
...
PMID:Binding of dynein light chain (PIN) to neuronal nitric oxide synthase in the absence of inhibition. 980 72
Cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and
inducible nitric oxide synthase
-2 (NOS-2) each have an important role in angiogenesis. The expression of these genes was investigated in human prostate cancer by immunohistochemistry, the expression of COX-1 and COX-2 being confirmed by mRNA analysis. Prostate cancer specimens from 12 patients were compared to control prostates from 13 patients operated on for bladder carcinoma. The intensity of COX-2 and NOS-2 immunostaining was significantly stronger in prostate cancer cells than in the non-malignant glandular epithelium of the control prostates. COX-2 and NOS-2 were clearly also expressed in the lesions of
prostatic intraepithelial neoplasia
(
PIN
) in control prostates. COX-2 was detected in the muscle fibres of the hyperplastic stroma of some control prostates. No significant difference was detected in COX-1 expression between control and cancer prostates. These results indicate that the expression of COX-2 and NOS-2 is elevated in prostatic adenocarcinoma and in
PIN
.
...
PMID:Increased expression of cyclooxygenase-2 and nitric oxide synthase-2 in human prostate cancer. 1131 Feb 11